The overall aim of my research is to enhance our understanding of neural tolerance development to ethanol in order to gain insight into the mechanisms underlying this phenomenon. Ethanol exposure produces alterations in neuronal functioning and tolerance develops when the brain changes to compensate for disruptions in behavior and function. The proposed studies will use electrophysiological techniques to examine tolerance development in calcium activated potassium and voltage gated calcium channels in the magnocellular neurons of the rat supraoptic nucleus and their corresponding nerve terminals in the posterior pituitary (HNS system). The HNS system is a model system because; (1) there are few preparations in which it is possible to directly relate the behavioral consequences of ethanol to underlying molecular mechanisms, (2) extensive studies have been done examining the acute effects of ethanol in the ion channels of the HNS system before and after chronic ethanol exposure, and (3) regional differences can be easily explored. Results from these studies will provide insights into the mechanisms underlying tolerance development and illuminate how cellular domains vary in their contribution to tolerance development.